Residency · Residency · Geriatrics

Osteoporosis and Fracture Prevention in the Elderly

Introduction

Osteoporosis affects approximately 10 million Americans, with an additional 44 million having low bone density classified as osteopenia. The lifetime fracture risk following age 50 is approximately 50 percent for women and 20 percent for men, making osteoporotic fractures one of the most common and consequential conditions in geriatric medicine. Hip fractures account for approximately 300,000 cases annually in the United States, carrying a devastating 20 to 30 percent one-year mortality rate and leaving only 40 to 60 percent of survivors able to recover their prior level of mobility. Vertebral fractures are the most common type of osteoporotic fracture, yet 70 percent are clinically silent, and each vertebral fracture increases the risk of a subsequent vertebral fracture five-fold. Despite the enormous burden of disease, osteoporosis remains dramatically underdiagnosed and undertreated: only 20 to 25 percent of hip fracture patients receive osteoporosis treatment within one year of their fracture, representing a profound failure of secondary prevention.

Pathophysiology

Bone is a dynamic tissue undergoing continuous remodeling through a tightly coupled cycle of osteoclast-mediated resorption and osteoblast-mediated formation. Peak bone mass is achieved by age 25 to 30, with approximately 80 percent of peak bone mass determined genetically and the remainder influenced by nutrition, physical activity, and hormonal factors. After age 40, age-related bone loss proceeds at approximately 0.5 to 1 percent per year in both sexes.

In women, the menopausal transition triggers an accelerated phase of bone loss at 2 to 3 percent per year for the first 5 to 10 years following menopause, driven by estrogen withdrawal. Estrogen normally suppresses osteoclast activity by stimulating the production of osteoprotegerin (OPG) and inhibiting RANKL expression. Its loss leads to upregulation of RANKL, which binds to RANK on osteoclast precursors and promotes their differentiation and activation, resulting in a marked increase in bone resorption. In men, bone loss is more gradual, with testosterone decline contributing to osteoporosis alongside age-related factors. Men tend to experience trabecular thinning while maintaining cortical thickness, which explains their relatively later presentation with fractures.

The OPG/RANK/RANKL system represents the key molecular pathway governing bone remodeling. RANKL, produced by osteoblasts and osteocytes, activates RANK receptors on osteoclast precursors to promote osteoclast differentiation and bone resorption. OPG acts as a decoy receptor that neutralizes RANKL, thereby inhibiting resorption. This pathway is the therapeutic target of denosumab.

Diagnosis

DXA (Dual-energy X-ray Absorptiometry)

Dual-energy X-ray absorptiometry is the gold standard diagnostic modality for osteoporosis, measuring areal bone mineral density in grams per square centimeter at the hip and lumbar spine. Results are expressed as T-scores representing the number of standard deviations below the mean of a young adult reference population. A T-score of negative 1.0 or above is classified as normal. A T-score between negative 1.0 and negative 2.5 defines osteopenia. A T-score at or below negative 2.5 defines osteoporosis. Severe osteoporosis is defined as a T-score at or below negative 2.5 in the presence of a fragility fracture.

The femoral neck T-score is used for FRAX calculation, while the lowest T-score at either the hip or spine is used for diagnostic classification. The USPSTF recommends DXA screening for all women aged 65 and older and for younger postmenopausal women with risk factors. The International Society for Clinical Densitometry recommends screening men at age 70 or older, or at age 50 or older if risk factors are present. Monitoring intervals are typically every one to two years during treatment and every two to five years if untreated with stable bone mineral density.

FRAX (Fracture Risk Assessment Tool)

The FRAX algorithm, developed by the World Health Organization, predicts the 10-year probability of major osteoporotic fracture and hip fracture based on clinical risk factors including age, sex, body mass index, prior fracture, parental hip fracture history, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, alcohol consumption of three or more units daily, and optionally the femoral neck bone mineral density. US treatment thresholds endorsed by the National Osteoporosis Foundation recommend pharmacological treatment when the 10-year probability of a major osteoporotic fracture is 20 percent or greater, or the 10-year probability of a hip fracture is 3 percent or greater. Limitations of FRAX include its failure to account for fall risk, glucocorticoid dose, number of prior fractures, and lumbar spine bone mineral density.

Vertebral Fracture Assessment (VFA)

Vertebral fracture assessment is performed using lateral spine imaging on the DXA scanner and is indicated for patients with a T-score below negative 1.0 and age 70 or older for women or 80 or older for men, height loss exceeding 4 centimeters, prior vertebral fracture, or glucocorticoid use. This assessment is important because the detection of prevalent vertebral fractures significantly alters treatment decisions.

Laboratory Evaluation

Laboratory evaluation is directed at excluding secondary causes of bone loss. Standard studies include a complete blood count, comprehensive metabolic panel (calcium, phosphorus, alkaline phosphatase, renal function), 25-hydroxyvitamin D level, thyroid-stimulating hormone, and intact parathyroid hormone. Additional testing should be considered based on clinical suspicion, including serum and urine protein electrophoresis to exclude multiple myeloma, celiac screen (tissue transglutaminase IgA), 24-hour urine calcium, cortisol, and testosterone in men.

Bone turnover markers, specifically C-telopeptide (CTX, a marker of resorption) and P1NP (procollagen type 1 N-propeptide, a marker of formation), are useful for monitoring treatment response, with a change of greater than 30 percent considered clinically significant.

<image>A diagnostic algorithm for osteoporosis evaluation. Start with "Risk Assessment" leading to DXA screening criteria (women ≥65, men ≥70, or younger with risk factors). Show DXA results branching into three pathways based on T-score: Normal (≥-1.0) → reassess in 5-10 years; Osteopenia (-1.0 to -2.5) → calculate FRAX → if above threshold treat, if below monitor; Osteoporosis (≤-2.5) → treat. Include a separate pathway for fragility fracture → treat regardless of BMD. Show the laboratory workup panel to exclude secondary causes. Include FRAX treatment thresholds (≥20% MOF or ≥3% hip) in a highlighted box. Add a side panel showing the WHO T-score classification with a bell curve of BMD distribution and where each category falls on the curve.</image>

Non-Pharmacological Management

Calcium and Vitamin D

Calcium intake should target 1,000 to 1,200 mg per day from the combination of dietary sources and supplements, with dietary sources preferred. Intake should not exceed 1,500 mg per day, as higher doses have raised cardiovascular safety concerns in some meta-analyses, though data remain conflicting. Calcium carbonate requires gastric acid for absorption and should be taken with food; it contains 40 percent elemental calcium. Calcium citrate is absorbed independently of gastric acid and is therefore preferred for patients taking proton pump inhibitors or those with achlorhydria; it contains 21 percent elemental calcium.

Vitamin D should be supplemented at 800 to 2,000 IU per day, targeting a 25-hydroxyvitamin D level of 30 to 50 ng/mL. Vitamin D3 (cholecalciferol) is preferred over D2 (ergocalciferol) due to its longer half-life and greater effectiveness at raising serum levels. For severe deficiency below 10 ng/mL, a loading regimen of 50,000 IU weekly for 8 to 12 weeks followed by maintenance dosing is appropriate.

Exercise

Weight-bearing aerobic exercise including walking, dancing, and stair climbing should be performed for 30 minutes on most days. Resistance training improves bone mineral density at loaded skeletal sites and reduces fall risk. Balance training reduces falls by 20 to 40 percent. The LIFTMOR trial demonstrated that high-intensity resistance and impact training improved femoral neck and lumbar spine bone mineral density in postmenopausal women with low bone mass and was both safe and effective.

Fall Prevention

Multifactorial fall prevention programs are essential because fracture prevention requires both stronger bones and fewer falls. The combined approach to bone-strengthening and fall-reduction represents the most effective fracture prevention strategy.

Lifestyle Modifications

Smoking cessation is important because smoking is associated with a 1.5- to 2-fold increase in fracture risk. Alcohol should be moderated, as consumption of three or more drinks daily increases fracture risk. Hip protectors can reduce hip fracture risk in nursing home residents if compliance is adequate, though adherence remains a significant barrier.

Pharmacological Treatment

Antiresorptive Agents

Bisphosphonates — First-Line

Bisphosphonates bind to hydroxyapatite in bone matrix, are taken up by osteoclasts during resorption, and inhibit the enzyme farnesyl pyrophosphate synthase, leading to osteoclast apoptosis. Alendronate at 70 mg orally weekly reduces vertebral fractures by 47 percent and hip fractures by 51 percent, as demonstrated in the FIT trial. Risedronate at 35 mg orally weekly or 150 mg monthly reduces vertebral fractures by 41 percent and non-vertebral fractures by 39 percent. Zoledronic acid at 5 mg intravenously annually reduces vertebral fractures by 70 percent and hip fractures by 41 percent, as demonstrated in the HORIZON trial. Its advantages include assured adherence through annual dosing and avoidance of gastrointestinal issues; infusion requires at least 15 minutes with adequate pre-infusion hydration, and it is contraindicated when creatinine clearance is below 35 mL/min. An acute phase reaction with flu-like symptoms occurs in approximately 30 percent of patients after the first infusion, managed with acetaminophen or ibuprofen. Ibandronate at 150 mg orally monthly or 3 mg intravenously every three months reduces only vertebral fractures (with no hip fracture data) and is therefore less preferred.

Oral bisphosphonates must be taken on an empty stomach with 8 ounces of plain water, and the patient must remain upright for 30 to 60 minutes without eating, drinking, or taking other medications to prevent esophageal injury. Adverse effects include gastrointestinal symptoms (esophagitis, esophageal ulceration) with oral formulations and musculoskeletal pain. Rare but serious complications include atypical femoral fractures (subtrochanteric or diaphyseal fractures associated with prolonged use beyond 3 to 5 years, often preceded by prodromal thigh pain, with an incidence of 3.2 to 100 per 100,000 person-years) and osteonecrosis of the jaw (with a risk of 1 to 10 per 100,000 patient-years with oral bisphosphonates, much higher with intravenous oncologic doses; dental evaluation before starting treatment is recommended).

Drug Holidays

Bisphosphonate drug holidays should be considered after 3 to 5 years of oral bisphosphonate therapy or 3 years of intravenous zoledronic acid in patients at moderate fracture risk. The rationale is supported by the long skeletal half-life of bisphosphonates (exceeding 10 years), which produces a residual antiresorptive effect that persists during the holiday. High-risk patients (T-score at or below negative 2.5 or prior fracture) should continue treatment or switch to an alternative agent rather than taking a holiday. After 2 to 3 years of holiday, reassessment with repeat DXA and bone turnover markers should guide the decision to restart treatment. The 2023 ACP guidelines recommend treatment for 5 years followed by reassessment rather than indefinite therapy.

Denosumab (Prolia)

Denosumab is a fully human monoclonal antibody directed against RANKL that inhibits osteoclast formation and activity. Administered as 60 mg subcutaneously every 6 months, it reduces vertebral fractures by 68 percent, hip fractures by 40 percent, and non-vertebral fractures by 20 percent, as demonstrated in the FREEDOM trial. Its advantages include the absence of renal dose adjustment (making it suitable for patients with chronic kidney disease) and the convenience of subcutaneous injection, which improves adherence. Adverse effects include hypocalcemia (requiring adequate calcium and vitamin D supplementation), infections (urinary tract infections, cellulitis), and rare osteonecrosis of the jaw and atypical femoral fractures.

A critically important concern with denosumab is the rebound effect upon discontinuation: abrupt cessation causes rapid bone loss and a significantly increased risk of multiple vertebral fractures within 6 to 12 months. Denosumab should never be discontinued without transitioning the patient to a bisphosphonate. The recommended approach is to administer intravenous zoledronic acid 6 months after the last denosumab dose and confirm that CTX remains suppressed.

Anabolic Agents

Teriparatide (Forteo)

Teriparatide, recombinant parathyroid hormone fragment 1-34, stimulates osteoblasts preferentially over osteoclasts when administered intermittently (as opposed to the continuous parathyroid hormone elevation seen in hyperparathyroidism). Dosed at 20 mcg subcutaneously daily for up to 2 years, it reduces vertebral fractures by 65 percent and non-vertebral fractures by 53 percent. Its indications include severe osteoporosis, fracture occurring despite bisphosphonate therapy, glucocorticoid-induced osteoporosis, and very high fracture risk. Anabolic therapy must be followed by antiresorptive therapy after completion of the anabolic course, as gains in bone density are lost otherwise. The original black box warning for osteosarcoma based on rat studies was removed in 2020 after 20 years of post-marketing surveillance showed no signal in humans. Contraindications include Paget disease, unexplained elevation of alkaline phosphatase, prior skeletal radiation, open epiphyses, and pre-existing hypercalcemia.

Abaloparatide (Tymlos)

Abaloparatide, a parathyroid hormone-related peptide analog, is administered at 80 mcg subcutaneously daily for up to 2 years. The ACTIVE trial demonstrated reductions in vertebral fractures of 86 percent and non-vertebral fractures of 43 percent, with less hypercalcemia than teriparatide. As with teriparatide, antiresorptive therapy must follow completion of the anabolic course.

Romosozumab (Evenity)

Romosozumab is a monoclonal antibody against sclerostin that produces a unique dual action: simultaneously increasing bone formation and decreasing bone resorption. Administered as 210 mg subcutaneously monthly for 12 months (a time-limited course), it reduces vertebral fractures by 73 percent and clinical fractures by 36 percent versus alendronate, as demonstrated in the ARCH trial. However, romosozumab carries a black box warning for increased cardiovascular risk including myocardial infarction, stroke, and cardiovascular death, and is contraindicated in patients who have had a myocardial infarction or stroke within the preceding year. Careful cardiovascular risk-benefit assessment is required in patients with cardiovascular risk factors. Following the 12-month romosozumab course, transition to denosumab or bisphosphonate therapy is required to maintain the gains achieved.

<image>A treatment algorithm for osteoporosis in elderly patients organized as a decision tree. Start with "Osteoporosis Diagnosis Confirmed" and first assess fracture risk level. For MODERATE risk (T-score -2.5 to -3.0, no fracture): start oral bisphosphonate (alendronate or risedronate), reassess at 3-5 years for drug holiday. For HIGH risk (T-score <-3.0, or fragility fracture): consider initial anabolic therapy (teriparatide, abaloparatide, or romosozumab) for 12-24 months THEN transition to antiresorptive (bisphosphonate or denosumab). For VERY HIGH risk (multiple vertebral fractures, T-score <-3.5): romosozumab x12 months → denosumab. Show a SPECIAL CONSIDERATIONS box for: CKD (denosumab preferred if CrCl <35), glucocorticoid-induced (teriparatide first-line for high risk), and denosumab discontinuation protocol (must transition to bisphosphonate). Include time-limited therapy durations and monitoring schedule (DXA every 1-2 years, CTX/P1NP at baseline and 3-6 months). Highlight the sequential therapy concept with arrows showing anabolic → antiresorptive transition.</image>

Special Considerations in Geriatric Patients

Fracture Liaison Services (FLS)

Fracture Liaison Services provide systematic identification, investigation, and treatment of patients presenting with fractures. These programs reduce refracture rates by 30 to 40 percent and improve treatment initiation to over 80 percent. Currently, only 20 to 25 percent of fracture patients receive osteoporosis treatment, representing the "treatment gap" that FLS programs are designed to close. The International Osteoporosis Foundation's Capture the Fracture initiative establishes gold-star standards for FLS programs.

Osteoporosis in Men

Thirty percent of all hip fractures occur in men, and mortality after hip fracture is actually higher in men than in women (37 percent versus 20 percent at one year). Evaluation for secondary causes is particularly important in men and should include testosterone levels, assessment for alcoholism, glucocorticoid use, and screening for myeloma. Treatment with bisphosphonates (alendronate and zoledronic acid), denosumab, and teriparatide is effective and approved in men. Testosterone replacement is indicated only in hypogonadal men and does not substitute for osteoporosis-specific therapy.

Glucocorticoid-Induced Osteoporosis (GIOP)

Glucocorticoid-induced bone loss is rapid, with 6 to 12 percent bone loss occurring in the first year of glucocorticoid use, predominantly affecting trabecular bone. ACR guidelines recommend risk assessment and treatment initiation for all patients receiving prednisone at 2.5 mg or more daily for 3 months or longer. Teriparatide has been shown to be superior to bisphosphonates for glucocorticoid-induced osteoporosis in the trial by Saag and colleagues published in 2007.

CKD-Mineral Bone Disorder

DXA is less reliable in patients with chronic kidney disease stages 4 and 5 because adynamic bone disease and renal osteodystrophy confound interpretation. Bisphosphonates should be avoided when creatinine clearance falls below 30 to 35 mL/min. Denosumab can be used regardless of creatinine clearance but carries a risk of severe hypocalcemia in advanced CKD, requiring close calcium monitoring. Bone biopsy may be necessary to guide treatment decisions in advanced CKD.

Key Clinical Pearls

• The treatment gap is the biggest problem in osteoporosis — only 20-25% of hip fracture patients receive treatment; Fracture Liaison Services can close this gap
• Sequential therapy (anabolic first → antiresorptive) builds more bone than antiresorptive alone — consider for very high-risk patients
• NEVER abruptly discontinue denosumab — rebound vertebral fractures occur within 6-12 months; always transition to a bisphosphonate
• Bisphosphonate drug holidays (after 3-5 years) are appropriate for moderate-risk patients but NOT for high-risk patients (T-score ≤-2.5 or prior fracture)
• Romosozumab is the most potent available agent but carries a cardiovascular black box warning — avoid in patients with recent MI or stroke
• Osteoporosis treatment prevents fractures only if combined with fall prevention — both components are essential
• Vertebral fractures are often silent — consider VFA imaging in high-risk patients; each vertebral fracture increases subsequent fracture risk 5-fold

References

1. Black DM, Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2016;374(3):254-262.
2. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417-1427.
3. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756-765.
4. Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, et al. Pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults: a living clinical guideline from the American College of Physicians. Ann Intern Med. 2023;179(3):351-368.
5. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis — 2020 update. Endocr Pract. 2020;26(Suppl 1):1-46.

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